Lipid phosphate phosphatase-1 dephosphorylates exogenous lysophosphatidate and thereby attenuates its effects on cell signalling

被引:17
作者
Pilquil, C [1 ]
Singh, I [1 ]
Zhang, QX [1 ]
Ling, ZC [1 ]
Buri, K [1 ]
Stromberg, LM [1 ]
Dewald, J [1 ]
Brindley, DN [1 ]
机构
[1] Univ Alberta, Dept Biochem, Signal Transduct Res Grp, Edmonton, AB T6G 2S2, Canada
关键词
cAMP; cell division; EDG; receptors; mitogen-activated; protein kinase; phosphatidate; phosphohydrolase; phospholipase;
D O I
10.1016/S0090-6980(01)00101-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The serum-derived phospholipid growth factor, lysophosphatidate (LPA), activates cells through a family of G-protein-coupled EDG receptors. The present article examines the role of lipid phosphate phosphatase-1 (LPP-1, or phosphatidate phosphate 2A) in regulating cell activation by LPA. Over-expressing LPP-1 approximately doubled the rate of dephosphorylation of exogenous LPA by Rat2 fibroblasts. The amount of LPA dephosphorylation was restricted to less than 10% of the total exogenous LPA. Over-expression of LPP-1 attenuated cell activation as indicated by diminished responses including cAMP, Ca2+, activation of phospholipase D and ERK, DNA synthesis and cell division. LPP-1 therefore provides a novel level of regulation for controlling cell signalling by exogenous LPA. (C) 2001 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:83 / 92
页数:10
相关论文
共 37 条
[1]   Recombinant human G protein-coupled lysophosphatidic acid receptors mediate intracellular calcium mobilization [J].
An, SZ ;
Bleu, T ;
Zheng, YH ;
Goetzl, EJ .
MOLECULAR PHARMACOLOGY, 1998, 54 (05) :881-888
[2]   Characterization of a novel subtype of human G protein-coupled receptor for lysophosphatidic acid [J].
An, SZ ;
Bleu, T ;
Hallmark, OG ;
Goetzl, EJ .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (14) :7906-7910
[3]   Molecular cloning of the human Edg2 protein and its identification as a functional cellular receptor for lysophosphatidic acid [J].
An, SZ ;
Dickens, MA ;
Bleu, T ;
Hallmark, OG ;
Goetzl, EJ .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1997, 231 (03) :619-622
[4]   Molecular cloning and characterization of a novel human G-protein-coupled receptor, EDG7, for lysophosphatidic acid [J].
Bandoh, K ;
Aoki, J ;
Hosono, H ;
Kobayashi, S ;
Kobayashi, T ;
Murakami-Murofushi, K ;
Tsujimoto, M ;
Arai, H ;
Inoue, K .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1999, 274 (39) :27776-27785
[5]   Mammalian lipid phosphate phosphohydrolases [J].
Brindley, DN ;
Waggoner, DW .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (38) :24281-24284
[6]   Characterization and purification of neutrophil ecto-phosphatidic acid phosphohydrolase [J].
English, D ;
Martin, M ;
Harvey, KA ;
Akard, LP ;
Allen, R ;
Widlanski, TS ;
Garcia, JGN ;
Siddiqui, RA .
BIOCHEMICAL JOURNAL, 1997, 324 :941-950
[7]   Naturally occurring analogs of lysophosphatidic acid elicit different cellular responses through selective activation of multiple receptor subtypes [J].
Fischer, DJ ;
Liliom, K ;
Guo, Z ;
Nusser, N ;
Virág, T ;
Murakami-Murofushi, K ;
Kobayashi, S ;
Erickson, JR ;
Sun, GP ;
Miller, DD ;
Tigyi, G .
MOLECULAR PHARMACOLOGY, 1998, 54 (06) :979-988
[8]   SECRETORY PHOSPHOLIPASE A(2) GENERATES THE NOVEL LIPID MEDIATOR LYSOPHOSPHATIDIC ACID IN MEMBRANE MICROVESICLES SHED FROM ACTIVATED CELLS [J].
FOURCADE, O ;
SIMON, MF ;
VIODE, C ;
RUGANI, N ;
LEBALLE, F ;
RAGAB, A ;
FOURNIE, B ;
SARDA, L ;
CHAP, H .
CELL, 1995, 80 (06) :919-927
[9]  
Frankel A, 1996, CLIN CANCER RES, V2, P1307
[10]   A single receptor encoded by vzg-1/lpA1/edg-2 couples to G proteins and mediates multiple cellular responses to lysophosphatidic acid [J].
Fukushima, N ;
Kimura, Y ;
Chun, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (11) :6151-6156